Relation between the hypothalamic-pituitary-thyroid (HPT) axis and the hypothalamic-pituitary-adrenal (HPA) axis during repeated stress

Neuroendocrinology. 2005;81(3):183-92. doi: 10.1159/000087001. Epub 2005 Jul 11.


Previous work has indicated that acute and repeated stress can alter thyroid hormone secretion. Corticosterone, the end product of hypothalamic-pituitary-adrenal (HPA) axis activation and strongly regulated by stress, has been suggested to play a role in hypothalamic-pituitary-thyroid (HPT) axis regulation. In the current study, we sought to further characterize HPT axis activity after repeated exposure to inescapable foot-shock stress (FS), and to examine changes in proposed regulators of the HPT axis, including plasma corticosterone and hypothalamic arcuate nucleus agouti-related protein (AGRP) mRNA levels. Adult male Sprague-Dawley rats were subjected to one daily session of inescapable FS for 14 days. Plasma corticosterone levels were determined during and after the stress on days 1 and 14. Animals were killed on day 15, and trunk blood and brains were collected for measurement of hormone and mRNA levels. Repeated exposure to FS led to a significant decrease in serum levels of 3,5,3'-triiodothyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4). Stress-induced plasma corticosterone levels were not altered by repeated exposure to the stress. Despite the decrease in peripheral hormone levels, thyrotropin-releasing hormone (TRH) mRNA levels within the paraventricular nucleus of the hypothalamus were not altered by the stress paradigm. Arcuate nucleus AGRP mRNA levels were significantly increased in the animals exposed to repeated FS. Additionally, we noted significant correlations between stress-induced plasma corticosterone levels and components of the HPT axis, including TRH mRNA levels and free T4 levels. Additionally, there was a significant correlation between AGRP mRNA levels and total T3 levels. Changes in body weight were also correlated with peripheral corticosterone and TRH mRNA levels. These results suggest that repeated exposure to mild-electric foot-shock causes a decrease in peripheral thyroid hormone levels, and that components of the HPA axis and hypothalamic AGRP may be involved in stress regulation of the HPT.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological
  • Agouti-Related Protein
  • Animals
  • Chronic Disease
  • Corticosterone / blood*
  • Disease Models, Animal
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Hypothalamus / metabolism
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Pituitary-Adrenal System / physiopathology
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Psychological / blood
  • Stress, Psychological / physiopathology*
  • Thyroid Gland / physiopathology*
  • Thyrotropin-Releasing Hormone / genetics
  • Thyrotropin-Releasing Hormone / metabolism
  • Thyroxine / blood
  • Triiodothyronine / blood


  • AGRP protein, rat
  • Agouti-Related Protein
  • Intercellular Signaling Peptides and Proteins
  • Proteins
  • RNA, Messenger
  • Triiodothyronine
  • Thyrotropin-Releasing Hormone
  • Thyroxine
  • Corticosterone